Locally delivered rhTGF-beta(2) enhances bone ingrowth and bone regeneration at local and remote sites of skeletal injury

The purposes of the present study were to determine if recombinant human tr ansforming growth factor-beta-2 (rhTGF-beta (2)) enhances bone ingrowth int o porous-coated implants and bone regeneration in gaps between the implant and surrounding host bone. The implants were placed bilaterally for four we eks in the proximal humeri of skeletally mature, adult male dogs in the pre sence of a 3-mm gap. In three treatment groups of animals, the test implant was treated with hydroxyapatite/tricalcium phosphate (HA/TCP) and rhTGF-be ta (2) in buffer at a dose per implant of 1.2 mug (n = 6), 12 mug (n = 7), or 120 mug (n = 7) and placed in the left humerus. In these same animals, a n internal control implant treated only with HA/TCP and buffer was placed i n the right humerus. In a non-TGF-beta treated external control group of an imals (n = 7), one implant was treated with HA/TCP while the contralateral implant was not treated with the ceramic. In vitro analyses showed that app roximately 15% of the applied dose was released within 120 h with most of t he release occurring in the first 24 h. The TGF-beta treated implants had s ignificantly more bone ingrowth than the controls with the greatest effect in the 12 mug/implant group (a 2.2-fold increase over the paired internal c ontrol (P = 0.004) and a 4-fold increase over the external control (P < 0.0 01)). The TGF-<beta> treated implants had significantly more bone formation in the gap than the controls with the greatest effect in the 12 and 120 mu g groups (1.8-fold increases over the paired internal controls (P = 0.003 a nd P = 0.012, respectively) and 2.8-fold increases over the esternal contro ls (P < 0.001 and P = 0.001, respectively)). Compared to the external contr ols, the internal control implants tended to have more bone ingrowth (1.9-f old increase, P = 0.066) and had significantly more bone formation in the g ap (1.7-fold increase, P = 0.008). Thus, application of rhTGF-<beta>(2) to a porous-coated implant-stimulated local bone ingrowth and gap healing in a weakly dose-dependent manner and stimulated bone regeneration in the 3-mm gap surrounding the coutralateral control implant, a site remote from the l ocal treatment with the growth factor. (C) 2001 Orthopaedic Research Societ y. Published by Elsevier Science Ltd. All rights reserved.